title: Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling.
abstract: The vascular endothelium mediates the ability of blood vessels to alter their architecture in response to hemodynamic changes; however, the specific endothelial-derived factors that are responsible for vascular remodeling are poorly understood. Here we show that endothelial-derived nitric oxide (NO) is a major endothelial-derived mediator controlling vascular remodeling. In response to external carotid artery ligation, mice with targeted disruption of the endothelial nitric oxide synthase gene (eNOS) did not remodel their ipsilateral common carotid arteries whereas wild-type mice did. Rather, the eNOS mutant mice displayed a paradoxical increase in wall thickness accompanied by a hyperplastic response of the arterial wall. These findings demonstrate a critical role for endogenous NO as a negative regulator of vascular smooth muscle proliferation in response to a remodeling stimulus. Furthermore, our data suggests that a primary defect in the NOS/NO pathway can promote abnormal remodeling and may facilitate pathological changes in vessel wall morphology associated with complex diseases such as hypertension and atherosclerosis.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, Boyer Center for Molecular Medicine, New Haven, Connecticut 06536, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Rudic
authors.forename: E G
authors.initials: EG
authors.lastname: Shesely
authors.forename: N
authors.initials: N
authors.lastname: Maeda
authors.forename: O
authors.initials: O
authors.lastname: Smithies
authors.forename: S S
authors.initials: SS
authors.lastname: Segal
authors.forename: W C
authors.initials: WC
authors.lastname: Sessa
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism / Q000502:physiology*; D020212:Carotid Artery Injuries; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000098:blood supply / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase